Compounds

Abstract

The invention provides adamantane derivatives, a process for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy.

What is claimed is:  
     
       1. A compound of general formula                    
       wherein 
       x represents 1 or 2;  
       A represents an oxygen atom;  
       B represents a hydrogen or halogen atom;  
       R represents a phenyl, pyridyl, indolyl, indazolyl, pyrimidinyl or thienyl group, each of which may be optionally substituted by one or more substituents independently selected from a halogen atom or an amino, cyano, carboxyl, hydroxyl, nitro, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, —N(R 1 )—C(═O)—R 2 , —C(O)NR 3 R 4 , —NR 5 R 6 , C 3 -C 8 -cycloalkyl, 3- to 8-membered heterocyclyl, C 3 -C 8 -cycloalkyloxy, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkylsulphinyl or C 1 -C 6 -alkylsulphonyl group, or a C 1 -C 6 -alkoxy, C 1 -C 6 -alkylamino, phenoxy, benzyl, C 1 -C 6 -alkylthio or phenylthio group optionally substituted by one or more substituents independently selected from a halogen atom or an amino, cyano, carboxyl, hydroxyl, nitro, 1-pyrrolidinyl, 1-piperidinyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, (di)C 1 -C 6 -alkylamino, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl or one of the following groups:                    
       R 1  represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group; 
       R 2  represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 3  and R 4  each independently represent a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 5  represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 6  represents a C 3 -C 8 -cycloalkyl group and, additionally, a C 1 -C 6 -alkyl group when R 5  is not a hydrogen atom;  
       R 7  represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 8  represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 9  represents a hydrogen atom or a hydroxyl group; and  
       R 10  represents a hydrogen atom or a phenyl or imidazolyl group;  
       with the proviso that when R represents a substituted phenyl, indolyl or indazolyl group, the substituent or substituents present do not comprise an amido, carboxyl, (di)C 1 -C 6 -alkylamido or C 1 -C 6 -alkoxycarbonyl group in an ortho position; or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       2. A compound according to claim  1  wherein R represents a phenyl, pyridyl or indolyl group, each of which may be optionally substituted by one or two substituents independently selected from a fluorine, chlorine, bromine or iodine atom or an amino, hydroxyl, nitro, aziridinyl, pyrrolidinyl, C 1 -C 4 -alkyl, trifluoromethyl, —NR 5 R 6 , C 1 -C 4 -alkylsulphinyl or C 1 -C 4 -alkylsulphonyl group, or a C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, benzyl, C 1 -C 4 -alkylthio or phenylthio group optionally substituted by one or two substituents independently selected from a halogen atom or an amino, cyano, carboxyl, hydroxyl, 1-pyrrolidinyl, 1-piperidinyl, methyl, methoxy, dimethylamino, C 1 -C 4 -alkoxycarbonyl or one of the following groups:                    
     
     
       3. A compound according to claim  1  wherein R 5  represents a hydrogen atom or a C 1 -C 4 -alkyl group. 
     
     
       4. A compound according to claim  1  wherein R 6  represents a C 1 -C 4 -alkyl group when R 5  is not a hydrogen atom. 
     
     
       5. A process for the preparation of a compound of formula (I) as defined in claim  1  which comprises reacting a compound of general formula                    
       wherein x, A and B are as defined in formula (I), with a compound of general formula                    
       wherein R is as defined in formula (I) and L is a leaving group; and optionally forming a pharmaceutically acceptable salt or solvate thereof. 
     
     
       6. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in claim  1 , in association with a pharmaceutically acceptable adjuvant, diluent or carrier. 
     
     
       7. A process for the preparation of a pharmaceutical composition as claimed in claim  6  which comprises mixing a pharmaceutically acceptable adjuvant, diluent or carrier with a compound of general formula                    
       wherein 
       x represents 1 or 2;  
       A represents an oxygen atom;  
       B represents a hydrogen or halogen atom;  
       R represents a phenyl, pyridyl, indolyl, indazolyl, pyrimidinyl or thienyl group, each of which may be optionally substituted by one or more substituents independently selected from a halogen atom or an amino, cyano, carboxyl, hydroxyl, nitro, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkyl, —N(R 1 )—C(═O)—R 2 , —C(O)NR 3 R 4 , —NR 5 R 6 , C 3 -C 8 -cycloalkyl, 3- to 8-membered heterocyclyl, C 3 -C 8 -cycloalkyloxy, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkylsulphinyl or C 1 -C 6 -alkylsulphonyl group, or a C 1 -C 6 -alkoxy, C 1 -C 6 -alkylamino, phenoxy, benzyl, C 1 -C 6 -alkylthio or phenylthio group optionally substituted by one or more substituents independently selected from a halogen atom or an amino, cyano, carboxyl, hydroxyl, nitro, 1-pyrrolidinyl, 1-piperidinyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, (di)C 1 -C 6 -alkylamino, halo-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl or one of the following groups:                    
       R 1  represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 2  represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 3  and R 4  each independently represent a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 5  represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 6  represents a C 3 -C 8 -cycloalkyl group and, additionally, a C 1 -C 6 -alkyl group when R 5  is not a hydrogen atom;  
       R 7  represents a hydrogen atom or a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 8  represents a C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl group;  
       R 9  represents a hydrogen atom or a hydroxyl group; and  
       R 10  represents a hydrogen atom or a phenyl or imidazolyl group;  
       with the proviso that when R represents a substituted phenyl, indolyl or indazolyl group, the substituent or substituents present do not comprise an amido, carboxyl, (di)C 1 -C 6 -alkylamido or C 1 -C 6 -alkoxycarbonyl group in an ortho position; or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       8. A method of effecting immunosuppression which comprises administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in claim  1  to a patient in need thereof. 
     
     
       9. A method of treating rheumatoid arthritis which comprises administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in claim  1  to a patient in need thereof.